Biomedical subjects

J F Spear

Publications and source records attributed to J F Spear.

At least 19 recordsLinked to original sources

PubMed1998

Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart.

We used low temperature to slow ion channel kinetics and studied the electrophysiological effects of quinidine at different pacing rates in isolated rabbit hearts. Fifteen epicardial electrograms together with an endocardial monophasic action potential were recorded. Epicardial activation and local recovery times were measured. Arrhythmias together with the characteristics of their mode of induction and rate were analyzed by epicardial activation sequence mapping. In the presence of quinidine, arrhythmias consistent with both triggered activity and reentry were observed. At baseline, triggered activity was not inducible, even though at 25 degrees C the recovery time was greater than that in the presence of quinidine at 36 degrees C. Also, with quinidine, the incidence of triggered activity decreased at 30 and 25 degrees C. Therefore prolongation of the recovery time per se does not cause triggered activity. Quinidine's use-dependent effects on conduction and reverse use-dependent effects on recovery time were amplified by low temperatures. These findings can be understood in terms of the known temperature sensitivities of the kinetics of the membrane ion channels responsible for activation and recovery. The results demonstrate that temperature can be used as a tool to elucidate mechanisms of drug action.

Action Potentials↗

PubMed1997

Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts.

INTRODUCTION: How cell-to-cell electrical coupling influences an antiarrhythmic agent's effect on conduction is largely unknown. To investigate this, we evaluated the effects of procainamide on myocardial conduction at decreasing degrees of cell-to-cell electrical coupling induced by graded doses of heptanol. METHODS AND RESULTS: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocardial fiber orientation in Langendorff-perfused rabbit hearts. The effects of procainamide (15 mg/L) on conduction velocity were determined in the presence of increasing doses of heptanol (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated superfused rabbit myocardium, intracellular potentials were recorded in the presence of 15 mg/L procainamide and heptanol (1.0 mM). In the absence of heptanol, procainamide slowed conduction velocity. In the presence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and reversed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation. Heptanol had no effect on action potential amplitude or maximum rate of depolarization in the presence of procainamide. CONCLUSIONS: Procainamide's effect on conduction velocity is influenced by the underlying degree of cell-to-cell electrical coupling. The present model should be useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.

Action Potentials↗

PubMed1996

Effect of coronary perfusion of heptanol on conduction and ventricular arrhythmias in infarcted canine myocardium.

INTRODUCTION: Abnormal cellular coupling is a major constituent of the slow, dissociated conduction that supports ventricular tachycardia (VT) following myocardial infarction. Agents that modulate cellular coupling may exert either proarrhythmic or antiarrhythmic effects. METHODS AND RESULTS: The effects of modulating cellular coupling on conduction and susceptibility to inducible VT were studied in 11 dogs with healed left anterior descending (LAD) infarction. The LAD circulation was isolated and supplied with arterial blood via a constant-flow bypass system. Localized intracoronary infusion of heptanol, an agent with relatively specific effects on intracellular coupling, was performed using this bypass system. Heptanol produced dose-dependent changes in cardiac conduction, assessed by delayed local activation times in sinus rhythm (0.5 mM: 11.9% +/- 11.0% change, P = 0.005; 1.0 mM: 45.8% +/- 25.5% change, P = 0.0004) and slowed conduction velocity both transverse and longitudinal to fiber orientation. Sustained VT was not induced in any of the control animals. During infusion of 0.5 mM heptanol, uniform sustained VT was inducible in 4 of 11 animals (P = 0.027). During infusion of 1.0 mM heptanol, sustained VT was induced in only 1 of 9 animals. CONCLUSIONS: In the canine model of healed myocardial infarction, heptanol had a bimodal effect on susceptibility to inducible VT. Low-dose heptanol facilitated the induction of sustained VT, and high-dose heptanol had an antiarrhythmic effect. This suggests that agents that modulate coupling may significantly modify susceptibility to VT following myocardial infarction.

Alcohols↗

PubMed1993

Electrophysiologic recovery in postischemic, stunned myocardium despite persistent systolic dysfunction.

Previous investigators have hypothesized that myocardial "stunning" may result either from a primary impairment in excitation or from electromechanical dissociation. Thrombolytic therapy and angioplasty have increased the importance of understanding the electrophysiologic effects of brief ischemia followed by reperfusion. We investigated the electrophysiologic properties of mechanically dysfunctional stunned myocardium in 18 dogs anesthetized with pentobarbital (30 mg/kg, intravenously administered). After thoracotomy, the proximal anterior descending coronary artery was occluded for 15 minutes, which was followed by 20 minutes of reperfusion. At baseline, peak ischemia, and 20 minutes of reperfusion, local electrogram durations, activation times, and refractory periods were measured from 12 standardized sites within the ischemic and border zones. Echocardiographic percentage of systolic wall thickening confirmed normal preischemic and markedly reduced postischemic function in the investigated region. Despite the marked electrophysiologic abnormalities observed in the ischemic zone during ischemia, mean electrogram duration, calculated conduction velocity, and mean effective refractory period after 20 minutes of reperfusion had returned almost to baseline values 39.2 +/- 11.5 msec versus 37.2 +/- 12.1 msec, 0.65 +/- 0.15 m/sec versus 0.68 +/- 0.15 m/sec, and 134 +/- 14 msec versus 131 +/- 8 msec, respectively. Corresponding mean values within the ischemic border zone were similarly close to baseline values after reperfusion. There was no significant difference in local heterogeneity (coefficient of variation) within the ischemic or border zone after reperfusion versus baseline values. Although the postischemic electrophysiologic status returned to normal, systolic thinning and dyskinesis persisted in the region of measurement. The contractile dysfunction that results from reperfusion-induced injury can thus occur in the setting of apparent excitation-contraction uncoupling.

Analysis of Variance↗

PubMed1993

"Supernormal" conduction and excitability.

Electrocardiographic manifestation of "supernormal" conduction is defined as conduction that is more rapid than expected or presence of conduction when block is anticipated. It is not supernormal in the sense or being more rapid than normal. Therefore, the term relative supernormality or "supernormality" is more appropriate. The mechanism of "supernormal" conduction is conduction during a period of supernormal excitability and conduction associated with altered membrane potential. Some of the more common phenomena that are not dependent on conduction during the supernormal period but manifest better than expected conduction, thus simulating "supernormal" conduction, include dual AV nodal conduction, the "gap" phenomenon, "peeling back" of the refractory period, summation of subthreshold responses, diastolic phase 4 depolarization, and phasic autonomic influences.

Electrocardiography↗

PubMed1992

Effect of coronary perfusion of heptanol or potassium on conduction and ventricular arrhythmias.

Abnormalities in cellular coupling, modulated in part by intracellular gap junctions, have an important role in the genesis of reentrant arrhythmias in the setting of chronic myocardial infarction. The effects of heptanol, which has a relatively selective action on gap junctional resistance at low concentrations, and potassium, which primarily affects active membrane properties, were assessed using a localized intracoronary infusion system in 11 normal dogs in vivo. Both agents caused a dose-related slowing of conduction. Programmed stimulation during potassium infusion resulted in ventricular fibrillation in two of six animals treated with a low dose (5.0-5.5 meq/l) and five of six animals treated with a high dose (7.0-7.5 meq/l). During the infusion of 1.0 mM heptanol, uniform ventricular tachycardia was induced in four of eight animals. Infusion of heptanol, but not potassium, increased the susceptibility to presumably reentrant ventricular tachycardia in normal myocardium. This suggests that agents that affect cellular coupling may have markedly different arrhythmogenic consequences than agents that primarily alter active membrane properties.

Alcohols↗

PubMed1992

Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium.

Abnormalities of myocardial gap junction-mediated cell coupling have been implicated in cardiac arrhythmogenesis. The potential role of gap junctional dysfunction in the generation of reperfusion-induced arrhythmias is uncertain. The purpose of this study was to measure the effects of myocardial ischemia and reperfusion on gap junctional conductance (gj) between isolated ventricular myocytes. By using a new experimental model, myocyte pairs were isolated from Langendorff-perfused rabbit hearts 1) after 30 minutes of global normothermic ischemia followed by 30 minutes of reperfusion, 2) after 75 minutes of control perfusion, or 3) immediately after removal of the heart. Myocytes and myocyte pairs were studied using whole-cell recording techniques. Action potential characteristics of cells in all three groups were normal. Despite similar mean gj in all three groups (0.88 +/- 0.27, 1.15 +/- 0.18, and 1.24 +/- 0.25 microS, respectively; p greater than 0.05), the postischemic group was more widely distributed and had a significantly greater proportion of poorly communicating cell pairs than either control group (gj less than 25% of mean in eight of 15 myocyte pairs versus zero of 15 and one of 13, respectively; p less than 0.02). Thus, postischemic myocyte pairs represent a heterogeneous population of electrically coupled cells in which individual deficits in coupling are masked by a normal mean value. In the reperfused intact heart, local disturbances of cell coupling, similarly undetected by gross measures of conduction, could disrupt myocardial conduction and activation on a microscopic scale and thus enhance arrhythmogenicity.

Action Potentials↗

PubMed1990

Effect of cellular uncoupling by heptanol on conduction in infarcted myocardium.

Experiments were performed in vitro on six normal thin ventricular epicardial tissue strips and 10 strips removed from the infarcted regions of dogs 21-60 days after experimental myocardial infarction. Conduction was evaluated by mapping activation sequences at 40-45 sites over an area of 1 x 2 cm during pacing at a basic cycle length of 2,000 msec. The amplitude and length of recorded electrograms were also determined at each site. After control recordings, heptanol, which increases gap junctional resistance, was added to the tissue bath at concentrations ranging between 0.2 and 1.0 mM. In contrast to its effect on normal tissues, heptanol caused 75 of 260 previously active sites in the infarcted tissues to become inactive. The affected sites were located in areas of very slow conduction and/or adjacent to areas of preexisting conduction block. In addition, heptanol decreased the length and degree of fractionation of electrograms recorded in slowly conducting regions of the infarcted tissues. The magnitude of the decrease in electrogram length following heptanol was related to the degree of electrogram abnormality during control as reflected in the ratio of electrogram length to amplitude. Heptanol shortened electrograms by causing local conduction block, which eliminated some components of the fractionated electrograms. In an additional eight epicardial strips removed from the infarcted region, 0.5 mM heptanol had only a slight effect (10.7% decrease) on the maximum rate of membrane depolarization. Thus, heptanol does not act primarily by way of depressing the fast inward current. We conclude from heptanol's effects on conduction and electrogram characteristics that slow and dissociated conduction in the infarcted region is due to an abnormality in gap junctional distribution between surviving cells and/or an abnormality in individual gap junctional function.

Action Potentials↗

PubMed1989

Electrophysiological studies on cardiac catheter ablation.

Clinical and animal investigations have pointed out that high energy electrical shocks are associated with the development of cardiac arrhythmias and with variable success in permanent ablation. The effects of electrode configuration and location on the size of the recorded electrogram was investigated to help explain variable catheter ablation results. We analyzed the cellular effects of catheter ablation shocks and found depression of resting potential, action potential amplitude, dV/dt and action potential duration. The most severe effects were noted with high current densities in tissues located between the cathode and anode. Damage was worse nearest the cathode. Similar cellular studies were completed using argon laser photoablation. Again, there was a decrease in resting potential, action potential amplitude and dV/dt. Laser energy led to a more focal region of myocardium void of action potentials and the border zone of injury was smaller. We also investigated the effects of lower energy shocks (1 to 10 joule) on cardiac tissues. Using microelectrodes, we observed that the membrane potential can "hang up" at the depolarized levels for varying periods of time and that conduction is altered during this membrane "hang-up" period. The duration and membrane hang-up level correlated with shock intensity and shock duration. Sequential shocks resulted in additive membrane "hang-up". We believe that membrane hang-up may be associated with brief arrhythmias observed following catheter ablation since conduction, refractoriness and excitability are all altered.

Action Potentials↗

PubMed1989

Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study.

Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic current-based model of cardiac electrical propagation, that changes in axial resistivity can modulate how spatial dispersion of intrinsic action potential duration is manifest.

Action Potentials↗

PubMed1989

Activation patterns in healed experimental myocardial infarction.

The maximum amplitude of vector loops formed by summing orthogonally recorded bipolar electrograms has been shown to reflect the direction of activation in cardiac muscle. To investigate whether components of vector loops could provide information about different activation directions in local areas of myocardium, we correlated "instantaneous vectors" with isochronal activation patterns in an in vitro preparation of experimental myocardial infarction. In thirteen 3 mm x 3 mm regions studied (from 11 tissues), at least 16 microelectrode impalements with a minimum density of 0.8 mm between sites were made. In seven situations in which notched, irregular, and prolonged duration electrograms were present, vector loops pointed in the same general direction throughout their entire time course. In these preparations, microelectrode impalements demonstrated only a single major direction of activation. In five of six areas in which multidirectional vector loops were present, two or more separate local directions of activation corresponded to the directions of the vector loop. Instantaneous vectors were then used to analyze propagation patterns in vivo in 10 animals with 2-4-week-old experimental myocardial infarction. Of 150 sites in the 10 animals, 13% contained more than one major local direction of activation. In 11 markedly abnormal sites, electrograms were recorded during pacing from four sites around the recording probe. When comparing electrogram characteristics from the four sites, a mean difference of 5.9 mV in electrogram amplitude and 19.1 msec in electrogram duration (coefficient of variation, 27% for amplitude and 22% for duration) was found. In only two of the 11 sites was it found that the same number of activation directions occurred from all pacing sites. We conclude: 1) Instantaneous components of vector loops accurately represent local directions of cardiac activation at differing times. 2) Most areas of experimental myocardial infarction have only one major direction of activation despite the presence of abnormal electrograms. 3) In some regions, however, two major local directions of activation can be identified within a relatively local area. 4) Geometric activation patterns in experimental myocardial infarction are markedly dependent on initial activation direction.

Action Potentials↗

PubMed1988

Electrophysiologic studies on ventricular tachyarrhythmias in a chronic canine infarct model.

The development of a chronic canine infarct model has allowed us to (1) understand better the mechanisms of tachyarrhythmogenesis in infarction; (2) evaluate new antiarrhythmic regimens as well as other antitachycardia therapies, including cryoablation, laser ablation, pacing, and surgical techniques; (3) correlate directly the presence of low-level late potentials with myocardial activation in the presence of delayed and fractionated cardiac electrograms; and (5) evaluate critically our present methods of programmed electrical stimulation.

Animals↗

PubMed1988

A computer model of the electrogram: what causes fractionation?

Fractionated electrograms are frequently recorded during mapping studies in patients with coronary artery disease and ventricular tachycardia. The authors developed a computer model of electrogram generation based on the biophysics of volume conductor fields. They show that fractionated electrograms can be produced as otherwise uniform wavefronts of activation encounter regions of increased cellular coupling resistance. Because of this, local activation may not correspond to the largest or most rapid deflection in a polyphasic, fractionated electrogram.

Animals↗

PubMed1988

Differential effects of procainamide, lidocaine and acetylstrophanthidin on body surface potentials and epicardial conduction in dogs with chronic myocardial infarction.

Twenty-eight anesthetized mongrel dogs were studied 2 to 74 months after experimental myocardial infarction in order to examine the effects of procainamide, lidocaine and acetylstrophanthidin on conduction within the infarcted region and the way such effects relate to changes in body surface potentials and antiarrhythmic efficacy. In each animal, 100 to 200 QRS complexes in the X, Y, Z leads were signal averaged, vector summed and high pass filtered at 50 Hz. Susceptibility to ventricular arrhythmia was evaluated using routine programmed ventricular extrastimulation in the anesthetized open chest animal. Epicardial electrograms were sequentially recorded at 45 standard sites within the infarcted region and referenced to the beginning of the QRS complex. Of the three agents, only procainamide exhibited antiarrhythmic action whereas lidocaine and acetylstrophanthidin produced inconsistent effects. Procainamide prolonged the time at which activity in the epicardial electrographic recordings ended relative to the beginning of the body surface QRS complex. This effect was significantly greater in electrograms that ended late in the QRS complex in the control state than for those that ended earlier. Such preferential effect on more abnormal sites was reflected on the body surface as a greater effect of procainamide in prolonging the lower energy terminal portion of the signal-averaged QRS complex than the earlier high energy portion. In contrast, lidocaine significantly prolonged the time at which electrograms ended only for those relatively normal electrograms that ended early in the QRS complex in the control state. In the signal-averaged body surface QRS complex, lidocaine produced a small but significant prolongation of the early high energy portion of the QRS complex but no change in the late portion. Acetylstrophanthidin produced a significant prolongation in early-ending electrograms and, surprisingly, significantly shortened the end time of electrograms that ended late in the QRS complex in the control state. Such effects were not reflected, however, on the body surface because acetylstrophanthidin had no significant effect on either the early or the late portion of the QRS complex. It is concluded that procainamide's differential effect between early- and late-ending electrograms is detected on the body surface by a greater prolongation in the terminal portion of the QRS complex. The signal-averaged body surface QRS complex is less sensitive in detecting the more subtle effects on conduction caused by lidocaine and acetylstrophanthidin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Interaction of metoprolol and lidocaine on the ventricular fibrillation threshold in the anesthetized dog.

In the present study, we evaluated the antiarrhythmic interaction (s) of metoprolol and lidocaine in 16 dogs using the ventricular fibrillation threshold (VFT) method. The right ventricle was stimulated with a 100 Hz train of 12.4 ms pulses delivered after every eighth atrial paced beat at a basic cycle length of 300 ms. Lidocaine dosage was 2 mg/kg followed by a 70 micrograms/kg/min infusion and metoprolol dosage was a 75 micrograms/kg bolus. In Group 1, lidocaine was followed by metoprolol; in Group 2, first lidocaine then metoprolol and again lidocaine were given; and in Group 3, dogs received first metoprolol, then lidocaine, and subsequently metoprolol. Drug dose intervals were 45 min. In Group 1, lidocaine elevated the VFT to 149% +/- 20% and metoprolol to 204% +/- 30% of control, (p less than 0.01). In group 2, the VFT remained elevated after the second lidocaine administration (p less than 0.05 vs. Group 1). In Group 3, the VFT was increased by metoprolol to 227% +/- 30% of control (p less than 0.01). Interestingly, defibrillation induced by the combination of metoprolol and lidocaine occurred after 3.2 +/- 0.5 s in four out of 16 animals (p less than 0.05). This "chemical" defibrillation never occurred when only metoprolol or lidocaine alone was administered. Fibrillation was often more organized in the presence of the combination of metoprolol plus lidocaine, which might relate to the observed defibrillation associated with metoprolol plus lidocaine. In conclusion, the combination of metoprolol and lidocaine has no proarrhythmic effects and may enhance the electrical stability of the ventricles as measured by the VFT method.

Anesthesia↗

PubMed1988

Inducible sustained ventricular tachycardia 4 years after experimental canine myocardial infarction: electrophysiologic and anatomic comparisons with early healed infarcts.

We studied a group of 17 dogs 4 to 6 years after infarction produced by 2 hr occlusion of the anterior descending coronary artery followed by reperfusion. Dogs in this "late" infarct group were compared with a group of 24 dogs with "early" healed infarcts (2 to 24 weeks old). With signal-averaging techniques body surface potentials were recorded during sinus rhythm. After thoracotomy epicardial electrograms were recorded from 45 standardized sites within the infarcted region and characteristics of selected electrograms were compared with anatomic features of underlying myocardium. Epicardial recordings from the late infarct group demonstrated earlier local activation (p less than .001) and shorter electrogram duration (p less than .001) when compared with recordings from the early infarct group. There was less temporal dispersion of activation and electrogram duration among the 45 sites in dogs with late infarcts as measured by respective coefficients of variance (p = .007 and less than .001). With programmed stimulation six dogs in the late and eight in the early infarct group exhibited inducible sustained ventricular tachycardia. Mean cycle length of the tachycardia in dogs with late infarcts was significantly shorter (p = .035). Late potentials were notably less prominent in dogs in the late infarct group with ventricular tachycardia than in dogs in the early infarct group. Fewer abnormal electrophysiologic characteristics of late infarcts coincided with relatively less scar in the underlying myocardium. Moreover, the strength of electrophysiologic-anatomic correlations differed in late as opposed to early infarcts. The latter findings suggest long-term evolution of infarct anatomy. We conclude that a substrate for reentrant tachycardia is present in dogs 4 to 6 years after reperfused infarction. Conduction characteristics are less abnormal in these late healed infarcts and are associated with a shorter ventricular tachycardia cycle length and less pronounced late potentials on the body surface.

Animals↗

PubMed1988

Autonomic modulation of ventricular arrhythmia in cesium chloride-induced long QT syndrome.

To evaluate autonomic influence on arrhythmogenesis in an animal preparation of triggered activity, we gave increasing doses of cesium chloride (0.125 to 5.0 mmol/kg iv) to 24 dogs distributed equally among four protocols of autonomic intervention: control, total denervation, beta-blockade, and left stellate stimulation. All dogs underwent atrioventricular node ablation followed by ventricular pacing. A left ventricular endocardial monophasic action potential (MAP) catheter allowed for detection of "MAP early afterdepolarizations" (mEAD). mEAD amplitude was measured relative to MAP amplitude. Cesium chloride (CsCl) increased both MAP duration (132% after 0.125 mmol/kg to 188% after 1.0 mmol/kg; p less than .001) and mEAD amplitude (20% after 0.125 mmol/kg to 49% after 1.0 mmol/kg; p less than .001) in a dose-dependent fashion. All dogs exhibited ventricular ectopy at roughly equivalent doses (0.88 +/- 0.5 mmol/kg). Cesium's peak effect on MAP characteristics, sinus node automaticity, and systolic blood pressure coincided with the onset of sustained ventricular tachycardia (VT). Whereas control and denervated dogs developed VT after similar doses of CsCl (1.21 +/- 0.1 vs 1.12 +/- 0.14 mmol/kg; p = NS), none of the six beta-blocked dogs developed sustained VT. Conversely, those dogs having undergone stellate stimulation developed VT after smaller doses (0.58 +/- 0.34 mmol/kg; p less than .001) and with earlier onset (12 vs 30 sec; p less than .025). After 0.5 mmol/kg of CsCl, left stellate stimulation augmented relative mEAD amplitude compared with control (51% vs 38%; p less than .001), whereas beta-blockade had little effect (39% vs 38%; p = NS). Autonomic intervention as such can affect the arrhythmogenicity of CsCl and similarly alter MAP characteristics. Furthermore, as beta-blockade can prevent sustained arrhythmia without eliminating mEADs, autonomic tone appears to modulate the expression of mEADs as sustained VT.

Action Potentials↗

PubMed1988

Mechanisms of depressed conduction from long-term amiodarone therapy in canine myocardium.

Amiodarone therapy leads to a significant impairment in myocardial conduction, yet it causes only a modest decrease in the maximum rate of depolarization of the action potential (dV/dT). To determine whether the decrease in dV/dT solely accounts for the impaired myocardial conduction or whether passive membrane properties may also be involved, we studied 21 ventricular epicardial tissues from 14 beagles; six dogs received long-term treatment (3-6 weeks) of amiodarone orally, and the remaining dogs served as controls. Amiodarone therapy was associated with a decrease in conduction velocity (0.41 +/- 0.15 vs. 0.56 +/- 0.05 m/sec; p less than 0.01). There was a trend toward a decrease in dV/dT and a significant decrease in the space constant (0.69 +/- 0.27 vs. 1.05 +/- 0.25 mm; p = 0.01), of which the latter correlated closely with the decrease in conduction velocity measured in the amiodarone-treated tissues (r = 0.85, p less than 0.05). These data indicate that the decrease in myocardial conduction velocity caused by amiodarone is primarily due to effects on overall resistance to passive current flow rather than effects on the inward sodium current.

Action Potentials↗